Bovine Serum Amine Oxidase and Polyamine Analogues: Chemical Synthesis and Biological Evaluation Integrated with Molecular Docking and 3-D QSAR Studies.
Rino RagnoAnna MinariniEleonora ProiaAntonini LorenzoAndrea MilelliVincenzo TumiattiMarco FiorePasquale FinoLavinia RutiglianoRossella FioravantiTomoaki TaharaElena PacellaAntonio GrecoGianluca CanettieriMaria Luisa Di PaoloEnzo AgostinelliPublished in: Journal of chemical information and modeling (2022)
Natural polyamines (PAs) are key players in cellular homeostasis by regulating cell growth and proliferation. Several observations highlight that PAs are also implicated in pathways regulating cell death. Indeed, the PA accumulation cytotoxic effect, maximized with the use of bovine serum amine oxidase (BSAO) enzyme, represents a valuable strategy against tumor progression. In the present study, along with the design, synthesis, and biological evaluation of a series of new spermine (Spm) analogues ( 1-23 ), a mixed structure-based (SB) and ligand-based (LB) protocol was applied. Binding modes of BSAO-PA modeled complexes led to clarify electrostatic and steric features likely affecting the BSAO-PA biochemical kinetics. LB and SB three-dimensional quantitative structure-activity relationship (Py-CoMFA and Py-ComBinE) models were developed by means of the 3d-qsar.com portal, and their analysis represents a strong basis for future design and synthesis of PA BSAO substrates for potential application in oxidative stress-induced chemotherapy.
Keyphrases
- molecular docking
- structure activity relationship
- molecular dynamics simulations
- cell death
- randomized controlled trial
- poor prognosis
- signaling pathway
- locally advanced
- risk assessment
- radiation therapy
- current status
- transcription factor
- squamous cell carcinoma
- mass spectrometry
- cell cycle arrest
- case control
- binding protein
- data analysis
- rectal cancer
- chemotherapy induced